Orthopoxvirus VP37 protein (VP37)

The Orthopoxvirus VP37 protein is a viral envelope protein encoded by the F13L gene, highly conserved across all orthopoxviruses (including monkeypox, variola/smallpox, cowpox, and vaccinia). It possesses enzymatic activity (phospholipase) and is essential for acquiring a double-membrane envelope, enabling virion egress and efficient dissemination within the host. VP37 is the primary target of the antiviral drug tecovirimat, which inhibits its function and prevents the spread of infection. Drug resistance is a growing concern with some observed mutations in the VP37 gene. VP37 is not present in the human host, making it a highly specific target for antiviral therapy. Its mechanism is distinct from other viral enzymes, and combination or new inhibitors are sought to address potential resistance and expand therapeutic options.

Other names

P37 proteinVP37PF13 proteinF13L gene productEnvelope wrapping protein

Tecovirimat: binds and inhibits VP37, blocking interaction with cellular transport machinery (Rab9 GTPase, TIP47), preventing viral envelopment and egress from infected cells. Other inhibitors: act similarly by targeting VP37's catalytic or structural activity, hindering formation of extracellular virus.